Gut Microbiota Markers for Antipsychotics Induced Metabolic Disturbance in Drug Naïve Patients with First Episode Schizophrenia – A 24 Weeks Follow-up Study

Abstract

BackgroundWhile cardiometabolic adverse effects associated with antipsychotic treatment is an important clinical challenge, the underlying mechanisms are unknown. Here we investigated if changes in gut microbial composition associate with the metabolic disturbance induced by the risperidone treatment of schizophrenia.MethodsNinety-four first episode, drug naïve schizophrenia patients (SZ), and 100 healthy controls (HCs) were enrolled at baseline. Six metabolic parameters (glucose, homeostasis model assessment of insulin resistance (HOMA-IR), Total cholesterol (Total-C), Low-density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol (HDL-C) and triglycerides) and body mass index (BMI) were measured for all participants. Gut microbial composition (microbials) was determined by fecal samples using 16S ribosomal RNA sequencing. Both the metabolic parameters and the gut microbiota were analyzed at baseline (all participants) and after 12 and 24 weeks of risperidone treatment (patients).ResultsThe glucose was significantly higher in SZ than HCs at baseline (p = 0.005). After 24-weeks treatment with risperidone, the levels of BMI, glucose, HOMA-IR, Total-C, LDL-C, HDL-C and triglyceride, were significant changed compared to baseline (p < 0.01). Six microbials showed significant changes in abundance after 24 weeks of risperidone treatment in SZ (p < 0.05), and four of these (Bacteroidetes, Proteobacteria, Christensenellaceae, and Enterobacteriaceae) were associated with the changes in metabolic parameters (p < 0.05). At baseline, the abundance of the microbials Christensenellaceae and Enterobacteriaceae were significantly associated with changes in triglyceride, BMI and HOMA-IR after 24-week risperidone treatment.ConclusionsChanges in gut microbial composition induced by risperidone treatment may be a key pathway underlying the metabolic disturbances observed in SZ patients. While these findings warrant replication in independent samples, they provide insight into the role of microbiota in SZ treatment, which can form the basis for development of better SZ treatment strategies.

Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review

“…41 Another study reported that risperidone treatment for 24 weeks caused a significant change in the abundance of Bacteroidetes, Christensenellaceae, Enterobacteriaceae, and Proteobacteria, which was associated with the changes in metabolic parameters such as increased BMI, HOMA-IR, and serum lipids. 81 On the contrary, 6 weeks of olanzapine treatment in an observational study caused significant weight gain but did not change the GMB composition in SCZ patients. 54 In a nutshell, the GMB could be regarded as a potential player in metabolic perturbations associated with AP treatment.…”

“…Li et al 81 Country: China Study design: 94 drug naïve, first-episode SCZ patients and 100 HCs were enrolled in the study. Metabolic parameters such as BMI, fasting blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol, insulin, and HOMA-IR were measured.…”

Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review

“…Chronic use of RIS led to an increase in the subjects' body mass index (BMI) and a significantly lower ratio of Bacteroidetes to Firmicutes compared to the control group. Li et al (2021) observed that after 24 weeks of RIS treatment, BMI, glucose, Homeostatic Model Assessment (HOMA-IR), Total-cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride levels were significantly changed compared to pre-treatment values. It was also found that the baseline abundance of Christensenellaceae and Enterobacteriaceae was significantly associated with changes in triglycerides, BMI and HOMA-IR after 24 weeks of RIS treatment.…”